PROJECT SUMMARY Decades of research suggest nicotine is the primary psychoactive constituent of tobacco that results in dependence. Consistent with this extensive literature and their regulatory authority to reduce (but not eliminate) nicotine, the Food and Drug Administration has identified nicotine products standards that target the appeal and addictiveness of cigarettes as a top research priority. Evidence to date suggests that smokers who are switched to reduced nicotine cigarettes reduce the number of cigarettes they smoke, reduce their exposure to nicotine and toxicants, and report less cigarette dependence. However, the implications of these observations are complicated by the fact that few smokers actually quit smoking and most supplement their use of reduced nicotine cigarettes with commercially available, non-study cigarettes that contain normal amounts of nicotine. If normal nicotine content cigarettes were largely unavailable as a result of regulation, many smokers may turn to alternative products, particularly e-cigarettes. The degree to which e-cigarettes facilitate further reductions in smoking, or cessation, will likely depend on characteristics of e-cigarettes that impact their reinforcing effects relative to conventional cigarettes. In particular, both nicotine concentration and availability of a variety of flavors may affect the degree to which e-cigarettes substitute for cigarettes. Consequently, Project 2 examines how three factors ? the nicotine content of cigarettes, the nicotine concentration of e-cigarettes, and the availability of both tobacco and non-tobacco flavors of e-cigarettes interact to determine whether current smokers reduce or stop smoking. Participants (N=480) at two sites will be randomized in a 2x2x2 design to receive A) cigarettes with 0.4 mg/g vs. 15.8 mg/g nicotine; B) e-cigarettes in tobacco only vs. tobacco and non-tobacco flavors; and C) e-cigarettes with 2 vs. 18 mg/ml nicotine. For 7 weeks, participants will be given a full supply of both cigarettes and e-cigarettes. During the last week, participants will be given monetary incentives to abstain from smoking tobacco. Equal numbers of younger (18-24) v. older (25+) and male v. female smokers will be recruited. We hypothesize that reducing nicotine in cigarettes will reduce cigarettes smoked, cigarette dependence, and exposure to toxicants while increasing use of e-cigarettes and the ability to abstain from smoking. We further predict that these effects will be greater when participants are provided e-cigarettes with higher nicotine concentration and both tobacco and non-tobacco flavors. We will also test the impact of condition on the subjective effects of each product and explore whether the behavioral and subjective effects vary as a function of age and gender. In summary, the proposed study will provide the Food and Drug Administration with critically important information directly related to potential products standards for the nicotine content of combusted tobacco. The results will determine how reducing nicotine in cigarettes impacts tobacco product use and effects when e-cigarettes with different characteristics are available as alternatives. 0925-0001/0002 (Rev. 08/12) Page Continuation Format Page